The transferability of lipid loci across African, Asian and European cohorts.
Kuchenbaecker K., Telkar N., Reiker T., Walters RG., Lin K., Eriksson A., Gurdasani D., Gilly A., Southam L., Tsafantakis E., Karaleftheri M., Seeley J., Kamali A., Asiki G., Millwood IY., Holmes M., Du H., Guo Y., Kumari M., Dedoussis G., Li L., Chen Z., Sandhu MS., Zeggini E., Understanding Society Scientific Group None.
Most genome-wide association studies are based on samples of European descent. We assess whether the genetic determinants of blood lipids, a major cardiovascular risk factor, are shared across populations. Genetic correlations for lipids between European-ancestry and Asian cohorts are not significantly different from 1. A genetic risk score based on LDL-cholesterol-associated loci has consistent effects on serum levels in samples from the UK, Uganda and Greece (r = 0.23-0.28, p < 1.9 × 10-14). Overall, there is evidence of reproducibility for ~75% of the major lipid loci from European discovery studies, except triglyceride loci in the Ugandan samples (10% of loci). Individual transferable loci are identified using trans-ethnic colocalization. Ten of fourteen loci not transferable to the Ugandan population have pleiotropic associations with BMI in Europeans; none of the transferable loci do. The non-transferable loci might affect lipids by modifying food intake in environments rich in certain nutrients, which suggests a potential role for gene-environment interactions.